Coriolus versicolor Detailed Scientific Review

1 Home Education and Research Resources for Professionals Clinical Tools and Resources Complementary/Integrative Medicine Education Resources Home Therapies Herbal/Plant Biologic TherapiesCoriolus versicolor Detailed Scientific ReviewOverview Background Mushrooms have been used for at least 5000 years for nutritional and medicinal purposes1,2. Anti-viral and anti- cancer effects have been demonstrated in more than 50 species through animal and in vitro studies. Six components of these mushrooms have been investigated for their activity in human cancers: the lentinan component of shiitake, schizophyllan, active hexose correlated compound (AHCC), maitake D-fraction and two components of Coriolus versicolor . According to the Review by Kidd, lentinan and schizophyllan have limited oral bioavailability, and the AHCC and maitake D-fractions are still in the early stages of investigation, but the two Coriolus versicolor components have been extensively investigated and show promise2.

2 Coriolus versicolor was first recorded during the Ming Dynasty of China3, and subsequently in a 1965 Japanese report of a patient with stomach cancer who benefited from drinking a tea, Saru-no-koshikake, that contained this mushroom. Subsequent laboratory and animal research identified the source of the tea s anti-tumor effects to be two polysaccharides*1,4-6. In 1989, two investigators at the U. S. National cancer Institute (Jong and Donovick7) published a Review of antitumor and antiviral substances from fungi including Coriolus versicolor . This Review noted seven studies and two U. S. patents issued for polysaccharides extracted from Coriolus versicolor . One extract was a polysaccharide-protein (proteoglycan) known as polysaccharide Kurcha (PSK or Krestin), and it had been found to be effective in the treatment of Ehrlich carcinoma and sarcoma 180 tumors in mice.

3 Furthermore, PSK had not exhibited any of the cytotoxicity or other side effects commonly seen with conventional anticancer treatment7. Subsequent laboratory and animal studies have further defined the antitumor, antimicrobial, antiviral and immune enhancing properties in both PSK and another protein-bound polysaccharide known as polysaccharide-protein complex (PSPC or PSP). Both substances are extracted by hot water from the mushroom s cultured mycelium (thread-like extensions)2,3,8,9. Mechanisms of Action: Polysaccharide Kurcha (PSK or Krestin) Prevention and cancer control properties of PSK have been associated with its antioxidant and free radical scavenging properties in vitro and in vivo9,10. PSK has demonstrated prevention of chemically induced DNA damage (sister chromatid exchanges)5 and subsequent tumors due to chemicals, radiation or other causes4,5.

4 PSK also seems to work in multiple steps of the malignant process by inhibiting adhesion, invasion, motility, and metastatic growth of tumor cells in animal models of cancer5,9. Adhesion and invasion are inhibited by suppression of cell matrix-degrading enzyme production by malignant cells. Motility of malignant cells and subsequent attachment to blood vessels are inhibited by suppression of tumor-cell induced platelet aggregation and anti-angiogenic factors4,10. PSK has also induced apoptosis (programmed cell death) in lymphoma, leukemia and pancreatic cells11,13. Immune responsiveness of the host does not appear to be affected by PSK under normal conditions, but immune systems depressed by tumor-burden or chemotherapy, have reportedly been restored to normal levels by PSK in animal studies1,9,14.

5 Immune restoration has included antibody and cytokine production and improvement of impaired antitumor activity of natural killer cells, T cells, macrophages and peripheral blood lymphocytes in vivo and in vitro4,9,15,18. PSK has also been demonstrated to inhibit the decline of immunocompetence during the perioperative period19 and inhibit the growth of residual tumors following cryoablation20. A variety of other mechanisms have been observed in laboratory studies of PSK. It was found to alter the expression of the p53 gene21, inhibit Epstein-Barr virus induced B-cell proliferation22 and suppress heat shock proteins that are thought to be involved in the progression of fibrosis10. PSK has also been observed to stimulate differentiation (orderliness) of human myeloblastic leukemic cells8. When injected directly into a tumor, PSK produces local inflammatory responses that result in the non-specific killing of tumor cells9.

6 One study on vaccine therapy against cancer found that PSK promotes the maturation of dendritic cells to produce IL-12 and Th1 type cytokines23; however, another study concluded that PSK was not as effective as OK432, a preparation of the bacteria Streptococcus pyogenes24. Mechanisms of Action: Polysaccharide-Peptide (PSP) Multiple and complex mechanisms of action of PSP have been demonstrated through in vitro and animal studies. PSP has suppressed the growth of human cancer cell lines in mice (sarcoma 180, lung adenocarcinoma and Lewis lung cancer )3,7,9. It has also inhibited incorporation of two structural units of DNA (uridine and thymidine) in Ehrlich ascites tumor cells, inhibited the growth of P388 leukemia cells, and demonstrated anti-proliferative activity against cell lines of human gastric cancer , lung cancer , lymphoma, and mononuclear leukemia3.

7 PSP has reversed tumor-induced immunodeficiencies in sarcoma-bearing mice by increasing immunoglobulin G and C3 complement levels9. It has also been associated with increases in white blood cell count, serum IgG, CD4, CD8, B-lymphocytes, and neutrophils, along with a higher survival rate of tumor bearing mice3. Many of these effects have been attributed to PSP being a strong scavenger of superoxide and hydroxyl radicals9,10. PSP has also been found to restrict the cell cycle of HL-60 leukemic cells through apoptosis26. These and other immune effects of PSK and PSP are described in reviews by Fisher and Yang10, Ooi and Liu9 and Chu, Ho and Chow14. Possible Toxicities of PSK and PSP PSK has been associated with side effects of gastrointestinal upset5 and darkeningof the fingernails, but these effects have been limited and general safety has been demonstrated with Page 1 of 14 CIMER - Coriolus versicolor Detailed Scientific Review - MD Anderson cancer Center4/24/2010 oral doses for extended periods of time2.

8 It does not seem to interact with hepatic drug-metabolizing enzymes involved in the chemical processing of most chemotherapy agents10, and no genetic damage has been detected by the Ames test5. At doses that produced necrotic changes in tumor cells, PSP produced no lesions in the vital organs of tumor-bearing mice after treatment for two months. It has not been associated teratogenic effects in mice or rats3. Human Trials of PSK and PSP All trials of PSK have been in combination or supplemental to chemotherapy and/or radiation. These trials have included numerous randomized, but non-blinded, clinical trials in Japan where it has been approved as an adjuvant (supplementary) treatment for digestive system, lung and nasopharyngeal cancers10. PSP has had fewer trials, all of them in China3. Designs and results of these human trials are reviewed in the Summary of Research.

9 *Polysaccharide Polysaccharides are composed of groups of interconnected monosaccharides (single sugars) and are a structurally diverse group that occurs widely in nature. Unlike the nucleotides in nucleic acids and amino acids in proteins that can only be interconnected in one way, polysaccharides can be interconnected at several points to form a wide variety of branched or linear structures. The number of possible permutations for four different monosaccharides can be up to 35,560 unique arrangements, while four amino acids can only form 24 different permutations. (Hodgson, J. Biotechnology, 1991, 9, 609-613, cited below.) Reference Ooi VE, Liu F. Immunomodulation and anti- cancer activity of polysaccharide-protein complexes. [ Review ] [179 refs]. Current Medicinal Chemistry. 2000 Jul;7(7):715-29.

10 Summary of Research Amount and Type of Research Based on our Review of the literature and other sources between September 1, 2002, and February 28, 2005, we have identified 41 references to " Coriolus versicolor ", "PSK", "Krestin" or "PSP", of which 32 (78%) were applicable to these terms and the treatment of cancer . A previous Review between October 1, 1997 and August 31, 2002, identified 59 references, of which 50 (85%) were applicable to cancer . Another previous Review of the literature ending in October of 1997 had identified 136 articles, of which 97 (71%) were applicable to cancer . Combining the results of these three reviews yields 236 articles, of which 179 (75%) are applicable to cancer . Of these, we have retrieved 163 articles as complete articles (reviews and human studies) or abstracts (animal and in vitro studies).